Defined morphological criteria allow reliable diagnosis of colorectal serrated polyps and predict polyp genetics

Criteria for the diagnosis of serrated colorectal lesions (hyperplastic polyp, sessile serrated adenoma without or with dysplasia—which we called mixed polyp—and traditional serrated adenoma) for which consensus has been reached should be validated for applicability in daily practice in terms of inter-observer reproducibility and their association with clinical features and (epi)genetic events. A study set was created from a consecutive series of colorectal polyps (n?=?1,926) by selecting all sessile serrated adenomas, traditional serrated adenomas and mixed polyps. We added consecutive series of hyperplastic polyps, classical adenomas and normal mucosa samples for a total of 200 specimens. With this series, we conducted an inter-observer study, encompassing ten pathologists with gastrointestinal pathology experience from five European countries, in three rounds in which all cases were microscopically evaluated. An assessment of single morphological criteria was included, and these were correlated with clinical parameters and the mutation status of KRAS, BRAF and PIK3CA and the methylation status of MLH1. Gender, age and localisation were significantly associated with certain types of lesions. Kappa statistics revealed moderate to good inter-observer agreement for polyp classification (κ = 0.56 to 0.63), but for single criteria, this varied considerably (κ = 0.06 to 0.82). BRAF mutations were frequently found in hyperplastic polyps (86 %, 62/72) and sessile serrated adenomas (80 %, 41/51). KRAS mutations occurred more frequently in traditional serrated adenomas (78 %, 7/9) and less so in classical adenomas (20 %, 10/51). Single morphological criteria for sessile serrated adenomas showed significant correlation with BRAF mutation (all p?≤?0.001), and those for classical adenomas or traditional serrated adenoma correlated significantly with KRAS mutation (all p?<?0.001). Therefore, single well-defined morphological criteria are predictive for genetic alterations in colorectal polyps.     

Periodontal inflamed surface area and C-reactive protein as predictors of HbA1c: a study in Indonesia

Periodontitis may exert an infectious and inflammatory burden, evidenced by increased C-reactive protein (CRP). This burden may impair blood glucose control (HbA1c). The aim of our study was to analyze whether periodontitis severity as measured with the periodontal inflamed surface area (PISA) and CRP predict HbA1c levels in a group of healthy Indonesians and a group of Indonesians treated for type 2 diabetes mellitus (DM2). A full-mouth periodontal examination, including probing pocket depth, gingival recession, clinical attachment loss, plaque index and bleeding on probing, was performed in 132 healthy Indonesians and 101 Indonesians treated for DM2. Using these data, PISA was calculated. In addition, HbA1c and CRP were analyzed. A validated questionnaire was used to assess smoking, body mass index (BMI), education and medical conditions. In regression analyses, it was assessed whether periodontitis severity and CRP predict HbA1c, controlling for confounding and effect modification (i.e., age, sex, BMI, pack years, and education). In healthy Indonesians, PISA and CRP predicted HbA1c as did age, sex, and smoking. In Indonesians treated for DM2, PISA did not predict HbA1c. Periodontitis may impair blood glucose regulation in healthy Indonesians in conjunction with elevated CRP levels. The potential effect of periodontitis on glucose control in DM2 patients may be masked by DM2 treatment. Clinical relevance: periodontitis may impair blood glucose control through exerting an inflammatory and infectious burden evidenced by increased levels of CRP.     

Autonomic regulation of organ vascular resistances during hypoxemia in the cat

This study aimed to dissect the roles played by the autonomic interoreceptors, the carotid bodies (cbs) and the aortic bodies (abs) on the vascular resistances of several organs in anesthetized, paralyzed, artificially ventilated cats challenged by systemic hypoxemia. Two 15 min challenges stimulated each of 5 animals in two different groups: (1) in the intact group hypoxic hypoxia (10% O₂ in N₂; HH) stimulated both abs and cbs, increasing neural output to the nucleus tractus solitarius (NTS); (2) in this group carbon monoxide hypoxia (30% O₂ in N₂ with the addition of CO; COH) stimulated only the abs, increasing neural output to the NTS. (3) In the second group in which their bilateral aortic depressor nerves had been transected only the cbs increased neural output to the NTS during the HH challenge; (4) in this aortic body resected group during COH neither abs nor cbs increased neural traffic to the NTS. CO and 10% O₂ reduced Hb saturation to the same level. With the use of radiolabeled microspheres blood flow was measured in a variety of organs. Organ vascular resistance was calculated by dividing the aortic pressure by that organ's blood flow. The spleen and pancreas revealed a vasoconstriction in the face of systemic hypoxemia, thought to be sympathetic nervous system (SNS)-mediated. The adrenals and the eyes vasodilated only when cbs were stimulated. Vasodilation in the heart and diaphragm showed no effect of chemoreceptor stimulated increase in SNS output. Different chemoreceptor involvement had different effects on the organs.     

Risk assessment and pathological reporting of gastrointestinal stromal tumour

Gastrointestinal stromal tumour (GIST) is the most common mesenchymal neoplasm of the GI tract. GISTs form a biological continuum ranging from benign incidentally detected minute lesions (stromal tumourlets) of no clinical significance to large and highly malignant sarcomatous neoplasms. The disease is characterized by indistinct borders between biologically different subsets within its spectrum leading to unpredictable course of the disease in the majority of cases. Availability of effective tyrosine kinase inhibitors underlined the urgent need for a reliable risk assessment system to reliably identify those patients who are at a significant risk for disease relapse and would thus profit from currently available effective targeted molecular therapy. While several risk systems have been established for GIST over the last decade, evidence is growing that no single system is optimal for all patients. Accordingly, an individualized risk system integrating classical parameters (site, size, mitotic index), status of serosal mechanical barrier covering the tumour (presence of tumour rupture or serosal penetration) as well as several other still debatable histological (coagulative necrosis, venous invasion, mucosal infiltration), biomarkers (proliferative index, p16 expression, etc.), and molecular (specific mutation types, adverse chromosomal aberrations, etc.) prognosticators would be of superb value for selecting the most appropriate patient treatment.     

Deep-seated huge hibernoma of soft tissue: a rare differential diagnosis of atypical lipomatous tumor/well differentiated liposarcoma

Background: Hibernoma is a rare benign fat-forming soft tissue tumor that differentiates similar to brown fat, hence an origin from remnants of fetal brown adipose tissue has been proposed. Mainly young adults are affected, usually without significant clinical symptoms. Material and methods: We report on four patients with hibernomas, who were treated at our hospital during the last 10 years. The clinicopathologic and immunohistochemical features are presented and treatment and follow-up data discussed. Results: Patients were 2 women and 2 men aged 21-67 years (mean: 45 yrs) who presented with a slowly growing, painless mass. The anatomic location was the thigh, upper arm, lateral thoracic wall and paravertebral soft tissue. Two of them were diagnosed preoperatively through a percutaneous core needle biopsy and the other two underwent surgery because of high clinical and radiological suspicion of liposarcoma. The tumor’s size ranged from 7 cm to 15.5 cm (mean: 11 cm). All were deep-seated subfascial intramuscular masses. Histologically, all four tumors were of the typical variant. All patients underwent a R0-surgical resection of the tumor and they were recurrence-free at last follow-up (mean: 47 months; range: 25-87). Conclusion: Hibernoma may present as huge deep intramuscular soft tissue mass in adults, closely mimicking well differentiated liposarcoma and should be considered in the differential diagnosis of fatty soft tissue tumors in any location. Surgical excision is the treatment of choice. The tumor has no malignant or recurrence potential.